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Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 415 records · Page 23Linked to original sources
PubMed1994

A novel form of congenital dyserythropoietic anemia associated with deficiency of erythroid CD44 and a unique blood group phenotype [In(a-b-), Co(a-b-)].

We have used a panel of well-characterized monoclonal antibodies (MoAbs) to examine the blood cells of a patient with a novel form of congenital dyserythropoietic anemia (CDA) characterized by intra-erythroblastic and intra-erythrocytic membranous inclusions. Twelve antibodies defining three nonoverlapping epitope groups on the extracellular domain of CD44 all failed to react with the red blood cells (RBCs) of the patient. A rabbit antibody to the cytoplasmic domain of CD44 from normal RBCs failed to react with the patient's RBC ghosts. In contrast, the patient's lymphocytes, granulocytes, and monocytes showed apparently normal CD44 expression. Bone marrow preparations stained with CD44 antibodies and visualized with 125I antimouse Ig (F(ab')2) followed by autoradiography showed positive staining of lymphocytes and myeloid cells but not of most orthotolidine-positive erythroblasts. The patient's RBCs also gave weaker than normal reactions with MoAbs of anti-LWab specificity while MoAbs to glycophorins A, B, and C, Rh polypeptides, CD47, CD55, CD58, CD59, acetylcholinesterase, and Lutheran and Kell glycoproteins all gave normal reactions. Agglutination tests with human blood grouping sera demonstrated that the RBCs of the patient have the unique phenotype In(a-b-), Co(a-b-) and that they also lack the high incidence RBC antigen AnWj. The phenotype In(a-b-) would be expected because these antigens are known to be expressed on CD44. There is also some evidence associating the AnWj antigen with CD44. However, the CO blood group locus is on chromosome 7p whereas that for CD44 is on chromosome 11p. Quantitative binding assays using 125I-labeled Fab fragments of CD44 antibodies did not show any evidence for reduced levels of CD44 on RBCs from the parents of the patient or from her unaffected sister. The parents and sister had the common Colton blood group phenotype [Co(a+b-)]. Neither deficiency of CD44 nor absence of Colton antigens are general features of CDA because erythrocytes from patients with CDA I, CDA II, CDA III, and two other unclassified CDAs had normal expression of CD44 and normal Colton blood group phenotypes. Further analysis of the defect(s) present in the patient's erythroid cells may provide useful information regarding membrane assembly and the regulation of differentiation in normal erythroid cells.

Anemia, Dyserythropoietic, Congenital↗
PubMed1994

Hepatitis B virus infection, the immune response and hepatocellular carcinoma.

More than 250 million people worldwide are chronically infected with the hepatitis B virus (HBV) and have a 200-fold increased risk of developing hepatocellular carcinoma (HCC). This is one of the most common cancers in the world with a geographical distribution highest in areas where HBV is endemic. A number of molecular mechanisms have been proposed to explain this correlation including an acutely transforming viral oncogene; chromosomal aberrations due to HBV integration (i.e. deletions, translocations, duplications); activation of cellular proto-oncogenes; inactivation of cellular anti-oncogenes; and transactivation of cellular genes by HBV gene products. HCC usually develops only after 20-30 years of persistent HBV infection accompanied by hepatocyte necrosis, inflammation and regenerative hyperplasia. Because HBV is not directly cytopathic, liver injury must be immune mediated. Factors that predispose HBV-infected individuals to develop HCC are chronicity, an immune response and liver injury rather than a direct genetic event. Hepatic injury and continuous hepatocyte regeneration may allow an accumulation of multiple mutational events sufficient for the emergence of HCC. Pathways which lead to chronicity, the immune response during HBV infection, mechanisms of pathogenesis and methods to prevent HBV infection are all relevant to the development of HCC. Recent studies characterizing the humoral and cellular immune responses in patients chronically infected with HBV and transgenic mouse models of HBV-specific immune tolerance and pathogenesis are providing new insights into the complex association between HBV infection and HCC.

Animals↗
PubMed1994

Carpal tunnel syndrome among grocery store workers.

The California Department of Health Services evaluated carpal tunnel syndrome (CTS), a median nerve entrapment condition associated with forceful and repetitive wrist motion, among grocery store workers at a large California supermarket where a CTS cluster had been reported. Forceful and repetitive wrist motion was measured, in three exposure levels, through a job classification scheme based upon type of work tasks and average time per week spent performing these tasks. A medical questionnaire and measurements of median sensory nerve conduction were used to measure CTS. CTS prevalence was 23% based upon a sample of 56 participants drawn from a workforce of 69 employees. A relative risk of 8.3 (95% confidence interval 2.6-26.4) for a history of CTS-like symptoms between the high and low exposure level groups held up after adjustment for the potential confounders of age, sex, alcohol consumption, and high-risk medical history. It was concluded that the basic principles of good ergonomic design should be used to prevent or diminish the risk of musculoskeletal injury in the workplace.

Adult↗
PubMed1994

Lead exposure in a tank demolition crew: implications for the new OSHA construction lead standard.

The Federal Occupational Safety and Health Administration (OSHA) has recently extended the basic health and safety provisions of the OSHA lead standard for general industry to workers in the construction industry. In this report we describe a tank demolition worksite that midway through the project strengthened its lead exposure control activities to a level that approximated the current lead standard. Of 12 tested ironworkers and laborers who worked at the site before the change, zinc protoporphyrin levels increased and seven developed blood lead levels (BLL) > 50 micrograms/dL. After the change these workers' BLLs declined. Six workers hired after the change did not experience increases in zinc protoporphyrin and none developed BLL > 25 micrograms/dL. The experience at this worksite demonstrates the usefulness and feasibility of implementing the current lead standard in construction settings.

Adult↗
PubMed1994

Glucocorticoids stabilize HER-2/neu messenger RNA in human epithelial ovarian carcinoma cells.

Recent evidence suggests that HER-2/neu oncogene overexpression may have a direct role in the pathogenesis of ovarian cancer rather than being merely a prognosticator of poor disease outcome. The mechanisms regulating expression of the p185HER-2/neu growth factor receptor protein are poorly understood. Glucocorticoid receptors are present in tumor cells of almost 90% of ovarian cancers, and these hormones inhibit ovarian cancer cell growth. Glucocorticoid regulation of HER-2/neu expression was investigated using the SK-OV-3 human epithelial ovarian cancer cell line in which the HER-2/neu gene is amplified five- to eightfold. Cells cultured in the presence of 10(-9)-10(-5) M dexamethasone or hydrocortisone displayed a dose-dependent increase in HER-2/neu mRNA. To determine if this effect was due to stabilization of existing HER-2/neu transcripts or to new mRNA synthesis, cells were treated with actinomycin D and cycloheximide once steady-state levels of HER-2/neu mRNA had been reached. These studies demonstrated prolongation of the half-life of existing HER-2/neu transcripts in the presence of dexamethasone. No concomitant increase in the p185HER-2/neu receptor protein in response to dexamethasone could be demonstrated by Western blot or immunohistochemical analyses. Cellular proliferation was inhibited approximately 20% by the presence of dexamethasone. These data suggest that post-transcriptional regulatory mechanisms may play a role in modulating some of the biologic effects of the HER-2/neu oncogene.

Cell Division↗
PubMed1994

Steroid hormonal independence of HER-2/neu mRNA expression in four human ovarian carcinoma cell lines.

Overexpression of HER-2/neu, a 185-kDa tyrosine kinase growth factor receptor, in human ovarian cancers has been correlated with a poor prognosis for survival of the disease. Previous studies have demonstrated that dexamethasone (Dex) induces a dose-dependent increase in HER-2/neu mRNA levels in the ovarian cancer cell line SK-OV-3 by stabilizing the HER-2/neu message. We extended these studies to test whether estrogen (Es), progesterone (Pr), and Dex were capable of regulating HER-2/neu mRNA levels in the human ovarian cancer cell lines NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3. Southern blotting demonstrated that all four cell lines contained a single copy of the 12.5-kb HER-2/neu gene. Blotting techniques demonstrated low to barely detectable levels of HER-2/neu mRNA and protein in these cell lines. To determine whether steroids regulated HER-2/neu expression, all four ovarian cancer cell lines were cultured in the presence of 1 x 10(-7) M Es, Pr, or Dex and Northern blotting was completed. Unlike SK-OV-3 cells, the cell lines tested did not respond to the steroid treatments with alterations in their HER-2/neu mRNA levels. In conclusion, neither Es, Pr, nor Dex regulates HER-2/neu mRNA levels in NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3 ovarian cancer cells. Future therapeutic manipulations of HER-2/neu should not involve hormonal intervention.

Adenocarcinoma↗
PubMed1994

Genetic imprinting in the mouse: implications for gene regulation.

Genetic imprinting specifies a germline marking that subsequently results in the repression of one or other parental allele at some point in development. Genetic manipulations to generate maternal and paternal duplications of specific chromosome regions have been used to screen almost the entire mouse genome for evidence of imprinting. As a result, 15 imprinting effects involving 10 regions on 6 different chromosomes have been detected that range from early embryonic lethalities to various growth and developmental defects seen only after birth. Genes with important roles in development therefore appear to be involved. Diverse studies have identified four imprinted genes, all of which show monoallelic expression in some, but not necessarily all, tissues. A correlation with methylation is indicated but the pattern of methylation is not consistent for each of the genes; methylation is therefore unlikely to be the imprinting signal. Methods being used to identify further imprinted genes are summarized and some of the difficulties posed are indicated.

Animals↗
PubMed1994

Overview of the space environmental effects observed on the retrieved Long Duration Exposure Facility (LDEF).

The Long Duration Exposure Facility (LDEF), which encompassed 57 experiments with more than 10,000 test specimens, spent 69 months in low Earth orbit (LEO) before it was retrieved by the Space Shuttle in January 1990. Hundreds of LDEF investigators, after studying for over two years these retrieved test specimens and the onboard recorded data and systems hardware, have generated a unique first-hand view of the long term synergistic effects that the LEO environment can have on spacecraft. These studies have also contributed significantly toward more accurate models of the LEO radiation, meteoroid, manmade debris and atomic oxygen environments. This paper provides an overview of some of the many LDEF observations and the implications these can have on future spacecraft such as Space Station Freedom.

Aluminum↗
PubMed1994

Clinical application of infrared thermography in the diagnosis of appendicitis.

To determine the clinical usefulness of infrared skin temperatures in diagnosing appendicitis, the authors conducted a prospective study of 86 adult and pediatric emergency department (ED) patients presenting during a 4-month study period with acute right lower abdominal pain. Skin temperature readings (FirstTemp digital thermometer, Intelligent Medical Systems, Inc, Carlsbad, CA) were taken from the right lower abdominal quadrant and a corresponding position on the left. An unpaired t test was used to determine if there was a significant difference between the right and left lower quadrants in patients with appendicitis. Discharged patients were followed up by telephone to determine any subsequent morbidity. A total of 23 patients had appendicitis confirmed by surgery; 63 subjects had other medical diagnoses. There was no significant skin temperature differential between the lower abdominal quadrants in either patient group (0.0 degree C vs 0.1 degree C; P > .5). Three patients had a skin temperature on the right that was at least 1 degrees C warmer than on the left; none of these patients had appendicitis. The results suggest that infrared thermography is not a sensitive diagnostic test for acute appendicitis in the ED population.

Abdomen↗
PubMed1994

Efficacy of pseudoephedrine for the prevention of barotrauma during air travel.

STUDY OBJECTIVE: To determine the efficacy of decongestant prophylaxis in the prevention of symptoms of middle ear barotrauma (aerotitis media) during air travel. DESIGN: Prospective, parallel, double-blind, randomized trial. SETTING: Two commercial airports in Michigan. TYPE OF PARTICIPANTS: Two hundred fifty volunteers with a history of recurrent ear discomfort during air travel. INTERVENTIONS: Following randomization, each subject received 120 mg pseudoephedrine or placebo 30 minutes before flight departure. Recorded data included subject demographics, history of ear discomfort, and otologic examination. After arrival at their final destinations, volunteers were asked to complete a questionnaire and return it by mail to the investigators. Questions included the intensity and duration of otologic symptoms experienced while flying and possible drug side effects. MEASUREMENTS AND MAIN RESULTS: One hundred ninety subjects completed the study; 96 received 120 mg of pseudoephedrine and 94 received a placebo. The two treatment groups were similar with regard to age, sex, weight, and flight profile (P > .1). Ear discomfort was present in 32% (31 of 96) of those receiving pseudoephedrine versus 62% (58 of 94) of the control group (chi 2 = 15.34; P = .0001). Adverse effects were minimal; seven patients experienced drowsiness. CONCLUSION: Our results suggest that use of an oral decongestant before flying decreases the incidence of middle ear barotrauma associated with ambient pressure changes during air travel.

Adult↗
PubMed1994

FPTT is a low-incidence Rh antigen associated with a "new" partial Rh D phenotype, DFR.

BACKGROUND: Several Rh D phenotypes with partial D antigens are recognized. Some partial D antigens are associated with low-incidence Rh antigens. New partial D antigens are revealed by an atypical pattern of reactions with anti-D. STUDY DESIGN AND METHODS: The reactions of D variant cells with panels of monoclonal anti-D and with antibodies to low-incidence antigens were compared to those of known D categories to identify a new Rh D phenotype. The inheritance of partial D antigens was studied by Rh phenotyping of the families of the probands. Standard serologic methods were used and family data were analyzed. RESULTS: A new Rh D phenotype, to be called DFR, was identified in 17 probands, two of whom had made anti-D. The partial D antigen carries epD3, epD4, and epD9 and lacks epD8. The presence of other D epitopes is ambiguous; different answers were obtained for the same sample with different monoclonal anti-D of the same apparent epitope specificity. The immunoglobulin class of the anti-D was important: IgG were more successful than IgM monoclonal anti-D in detecting the partial D of DFR. Family studies showed that DFR traveled with Ce more frequently than with cE. The low-incidence antigen FPTT (International Society of Blood Transfusion number 700048) was found on all DFR samples. Family studies demonstrated that FPTT is, as suspected, part of the complex Rh system. CONCLUSION: The partial D of the Rh D phenotype, DFR, is recognized by its pattern of reactions with monoclonal anti-D and its association with the low-incidence antigen FPTT, FPTT has now been numbered Rh50.

Antibodies, Monoclonal↗
PubMed1994

Expression of complement regulatory molecules and other surface markers on neutrophils from synovial fluid and blood of patients with rheumatoid arthritis.

In an effort to elucidate the activation status of neutrophils (PMN) in inflammatory joint disease the expression of relevant cell surface proteins was examined using immunofluorescence and flow cytometry. Paired samples of SF and peripheral blood were obtained from 18 patients with RA and PMN purified using methods designed to minimize activation in vitro. We then used flow cytometry to measure expression of the four membrane complement regulatory molecules, decay accelerating factor (DAF; CD55), complement receptor 1 (CR1; CD35), membrane cofactor protein (MCP; CD46) and CD59; two adhesion molecules of the integrin family LFA1 (alpha chain, CD11a), complement receptor 3 (CR3; alpha chain, CD11b), and their common beta chain (CD18); the major receptor for immune complexes Fc gamma RIII (CD16), and the leucocyte common antigen tyrosine phosphatase (L-CA; CD45). Expression of these molecules was also measured on peripheral blood PMN from 18 age- and sex-matched normal controls. In RA, SF PMN expressed significantly higher levels of the complement regulators CD55 and CD35, the adhesion molecule CR3 (CD11b/CD18) and of CD45 but significantly lower levels of CD46 and CD11a in comparison with blood PMN from the same patient. Expression of CD59 and CD16 did not differ between the two groups. These changes may increase adhesiveness and complement resistance of PMN in SF compared with blood. PMN from RA expressed significantly less of all the complement C3 convertase regulators (CD55, CD46, CD35), all the adhesion molecules (CD11a, CD11b, CD18) and the phosphatase CD45 than did blood PMN from age and sex-matched control individuals.

Adult↗
PubMed1994

Loss of the normal relationships between growth hormone, growth hormone-binding protein and insulin-like growth factor-I in adolescents with insulin-dependent diabetes mellitus.

OBJECTIVE: It has been proposed that the dissociation between growth hormone secretion and insulin-like growth factor-I (IGF-I) concentrations in insulin-dependent diabetes mellitus arises because of partial resistance at the GH receptor. In order to explore this hypothesis further we have examined the relations between IGF-I, GH-binding protein (GHBP), and GH secretion in normal subjects and patients with diabetes during puberty. DESIGN AND SUBJECTS: Blood samples for the estimation of IGF-I and GHBP levels were obtained from 104 patients with diabetes and 89 puberty matched controls. Thirty-four of the controls and 42 of the patients with diabetes also underwent an overnight GH secretory profile with measurements of GH every 15-20 minutes between 2000 and 0800 h. RESULTS: In multivariate analysis using sex, puberty stage, and presence or absence of diabetes as dependent variables, diabetes was associated with increased GH levels (F = 23.04, P < 0.001), reduced IGF-I (F = 10.89, P < 0.001), and reduced GHBP levels (F = 31.36, P < 0.001). A negative relation between GH and GHBP levels (r = -0.44, P < 0.01) was found in normal subjects but this was absent in those with diabetes. Both GHBP and IGF-I levels in the diabetic subjects were correlated with total insulin dose (r = 0.4, P < 0.001, and r = 0.46, P < 0.001, respectively). Yet there was no direct correlation between GHBP and IGF-I concentrations. The variation in IGF-I levels was also related to glycosylated haemoglobin levels in the diabetics (r = -0.27, P = 0.01). In a stepwise multiple regression analysis insulin dose contributed 23%, HbA1 4.4% and C-peptide levels 3.7% to the variation in IGF-I levels. CONCLUSIONS: In adolescents with insulin dependent diabetes mellitus, the elevated GH concentrations are associated with low circulating IGF-I and GHBP concentrations and the normal reciprocal relation between GHBP and GH is no longer evident. Although IGF-I and GHBP are both related to insulin dose, there is no direct correlation between these variables. This may indicate that GHBP reflects GH receptor numbers but not necessarily post receptor events, and the weak positive correlation between GH and IGF-I indicates that increased growth hormone secretion may compensate for reduced receptor numbers.

Adolescent↗
PubMed1994

Reversibility of physiological growth hormone secretion in children with psychosocial dwarfism.

OBJECTIVE: Reversibility of GH insufficiency with a change of environment is characteristic of psychosocial dwarfism, and excludes an organic endocrinopathy. However, the change in GH pulsatility has not previously been described. We therefore wished to study spontaneous GH secretion before and after change to a more favourable environment in 11 children with psychosocial deprivation and short stature in order to evaluate if separation from the families can modify their patterns of GH secretion. PATIENTS AND DESIGN: We describe 11 prepubertal children (6 M and 5 F; 2.2-13.5 years of age) who had growth failure and psychosocial deprivation. They were diagnosed by a multidisciplinary team as having environmental growth failure after admission to hospital for 3 weeks. Six of them were discovered to have been sexually abused. During the uninterrupted hospital admission parental access was restricted. Three sets of 18-hour GH profiles were performed on each child, except one child who had only two, during the 3-week admission. MEASUREMENTS: Pulse analysis of GH profiles was by Fourier transformation. RESULTS: On the first day of admission spontaneous GH secretion demonstrated a spectrum of abnormalities in the pattern of basal values, pulse frequency and pulse amplitude. Such GH insufficiency showed reversibility during the 3 weeks in hospital. Indeed, there was a significant increase in GH secretion which was amplitude modulated without any significant modification in pulse frequency. CONCLUSION: Our data indicate that there is abnormal physiological GH secretion in children with psychosocial deprivation, which is associated with growth failure. Despite a pathological situation, each child retained his own characteristic pattern of GH pulsatility. The pattern of reversibility of abnormal GH pulsatility provides information for the mechanism of the control of GH secretion.

Adolescent↗
PubMed1994

The pathophysiology of the insulin-like growth factor axis in fetal growth failure: a basis for programming by undernutrition?

Recent evidence suggests that a number of adulthood conditions, including non-insulin dependent diabetes mellitus (NIDDM) and lipid and cardiovascular abnormalities are associated with intra-uterine growth retardation (IUGR). It is possible that this arises from programming of endocrine axes during development as a result of an adverse intra-uterine environment. Insulin-like growth factors (IGFs) are mitogenic polypeptides which stimulate cellular proliferation and differentiation and are important in human fetal development. The functions of IGFs are modulated by specific high affinity binding proteins (IGFBPs). IGFBP-1 is antagonistic to the insulin-like and growth promoting effects of IGF-I, and IGFBP-3 holds IGFs in the circulation by associating with IGFs and an acid labile subunit to form a ternary complex. Using specific radioimmunoassays and fetal serum obtained during diagnostic cordocentesis we have investigated the role of the IGF/IGFBP axis in human fetal development. In a study of 130 singleton pregnancies we have examined levels of immunoreactive IGFs and IGFBPs in normally grown fetuses (AGA), starved small fetuses affected by uteroplacental insufficiency (UPI), and non-starved small fetuses (SGA). IGF-I was significantly lower in the UPI group (n = 14, 7.8 +/- 0.6 micrograms l-1), than in either the SGA group (n = 22, 31.4 +/- 3.5 micrograms l-1, P = 0.0001) or the AGA group (n = 94, 36.3 +/- 1.9 micrograms l-1, P = 0.0001). IGFBP-3 showed similar changes (UPI: 682.6 +/- 50.0 micrograms l-1; SGA: 831.9 +/- 55.5 micrograms l-1; AGA: 847.7 +/- 19.8 micrograms l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗